Dose-ranging Safety and Tolerability Study in Subjects ≥60 Years of Age

A Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Oral Doses of CNP520 in Healthy Elderly Subjects

The study determined the safety of CNP520 in healthy elderly over 3 months. Data relevant for Pharmacokinetic/Pharmacodynamic modeling were obtained in order to define the target dose in subsequent efficacy studies.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: CNP520

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14050
    • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2333 CL
    • Novartis Investigative Site
  • GZ
    • Groningen, GZ, Netherlands, 9713
      • Novartis Investigative Site
• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Novartis Investigative Site
  • Mid Glamorgan, United Kingdom, CF484DR
    • Novartis Investigative Site
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT9 6AD
      • Novartis Investigative Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Novartis Investigative Site
    • Long Beach, California, United States, 90806
      • Novartis Investigative Site
  • Florida
    • Miami, Florida, United States, 33126
      • Novartis Investigative Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Healthy status
• Body weight: ≥45kg
• BMI: 18-34 kg/m2

Key Exclusion Criteria:

• History or presence of any clinically significant disease of any major system organ class.
• Heavy smoker status
• History /presence of clinically significant neurological or psychiatric disorders
• Any medical condition that might lead to or is associated with any cognitive deficit
• History or presence of severely impaired renal function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo to CNP520 was taken once daily (qd) orally for 13 weeks.	Drug: Placebo; Matching placebo to CNP520 was supplied in capsules.
Experimental: CNP520 2 mg; CNP520 2 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 10 mg; CNP520 10 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 35 mg; CNP520 35 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.
Experimental: CNP520 85 mg; CNP520 85 mg was taken qd orally for 13 weeks.	Drug: CNP520; Other Names: CNP520 was supplied as capsules in dose strengths of 1 mg, 10 mg, 25 mg and 75 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Non-serious and Serious Adverse Events (AEs) and Deaths	Safety monitoring was conducted throughout the study.	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Amyloid Beta (Aβ) 1-38 , Aβ 1-40 and Aβ 1-42 Cerebrospinal Fluid (CSF) Concentrations	CSF samples were collected by lumbar puncture for assessment.	Day 92
Summary of Plasma PK Parameter: Cmax	Cmax = the observed maximum plasma concentration following drug administration. Blood samples were collected to assess Cmax. The PK analysis set was used for the analysis.	Days 1, 91
Summary of Plasma PK Parameter: AUCtau	AUCtau = the area under the plasma concentration-time curve from zero to the end of the dosing interval tau. Blood samples were collected to assess AUCtau.	Days 1 and 91
Summary of Plasma PK Parameter: Tmax	Tmax = the time to reach the maximum concentration after drug administration. Blood samples were collected to assess Tmax.	Days 1 and 91
Summary of Plasma PK Parameter: Tlag	Tlag = time delay between drug administration and first observed concentration above the lower limit of quantification (LOQ) in plasma . Blood samples were collected to assess Tlag.	Days 1 and 91
Summary of Plasma PK Parameter: T1/2	T1/2 = the terminal elimination half-life. Blood samples were collected to assess T/12.	Day 91
Summary of PK Parameter: CLss/F	CLss/F = the apparent systemic clearance from plasma observed during a dosing interval at steady state following extravascular administration. Blood samples were collected to assess CLss/F.	Day 91
Summary of Plasma PK Parameter: Racc	Racc = the accumulation ratio . Blood samples were collected to assess Racc.	Day 91
Summary of CSF PK Concentrations	CSF samples were collected by lumbar puncture for assessment.	Days 1, 14, 28, 42, 56, 70 and 91
Area-under-plasma Concentration Time Curve up to Infinity (AUCinf)	CNP520 concentrations in plasma	Day 91
Apparent Volume of Distribution (Vz/F)		Day 91

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2015
• Primary Completion (Actual): March 11, 2016
• Study Completion (Actual): March 11, 2016

Study Registration Dates

• First Submitted: August 18, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimate): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): August 11, 2017
• Last Update Submitted That Met QC Criteria: August 7, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Alzheimer's Disease,; Amyloid Beta,; cerebrospinal fluid,; beta secretase
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; CNP520
• Other Study ID Numbers: CCNP520X2102; 2013-005576-18 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No